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Aims: Pathophysiology of atrial fibrillation (AF) remains unclear. Interactions between scar and conduction velocity (CV) and their impact on wavefront propagation in sinus rhythm (SR) and rotational activity burden in AF were evaluated., Methods and Results: Local activation times (LATs) and voltage data were obtained from patients undergoing ablation for persistent AF. Omnipolar voltage (OV) and bipolar voltage (BV) data were obtained during AF and SR at pacing intervals of 600 and 250 ms. Local activation times were used to determine CV dynamics and their relationship to the underlying voltage and pivot points in SR. Computational modelling studies were performed to evaluate the impact of CVs and fibrosis on rotational activity burden in AF. Data from 60 patients with a total of 2 768 400 LAT and voltage points were analysed (46 140 ± 5689 points/patient). Voltage determined CV dynamics. Enhanced CV heterogeneity sites were predominantly mapped to low-voltage zones (LVZs) (0.2-0.49 mV) (128/168, 76.2%) rather than LVZs (<0.2 mV) and frequently co-located to pivot points (151/168, 89.9%). Atrial fibrillation OV maps correlated better with SR BV 250 ms than 600 ms maps, thereby representing fixed and functional remodelling. Sinus rhythm maps at 250 ms compared with 600 ms harboured a greater number of pivot points. Increased CV slowing and functional remodelling on computational models resulted in a greater rotational activity burden., Conclusion: Conduction velocity dynamics are impacted by the degree of scar. Conduction velocity heterogeneity and functional remodelling impacts wavefront propagation in SR and rotational activity burden in AF. This study provides insight into the pathophysiology of AF and identifies potential novel ablation targets., Competing Interests: Conflict of interest: R.J.H. has received research grants, educational grants, and speaker’s fees from Biosense Webster, Medtronic, and Abbott. P.D.L. receives speaker fees and research grants from Medtronic, Abbott, and Boston Scientific. S.H. has received speaker’s fee from Abbott. S.H. and R.J.H. are inventors of the STAR mapping system and are shareholders in Rhythm AI Ltd. S.H. is a British Heart Foundation Clinical Intermediate Fellow and receives a grant from the British Heart Foundation. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated., Methods and Results: Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified., Conclusion: Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF., Competing Interests: Conflict of interest: R.J.H. has received research grants, educational grants, and speaker’s fees from Biosense Webster, Medtronic, and Abbott. P.D.L. receives speaker fees and research grants from Medtronic, Abbott, and Boston Scientific. S.H. has received speaker’s fee from Abbott. S.H. and R.J.H. are shareholders in Rhythm AI Ltd. S.H. is a British Heart Foundation Clinical Intermediate Fellow and receives a grant from the British Heart Foundation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Atrial fibrillation (AF) is sustained by re-entrant activation patterns. Ablation strategies have been proposed that target regions of tissue that may support re-entrant activation patterns. We aimed to characterize the tissue properties associated with regions that tether re-entrant activation patterns in a validated virtual patient cohort., Methods and Results: Atrial fibrillation patient-specific models (seven paroxysmal and three persistent) were generated and validated against local activation time (LAT) measurements during an S1-S2 pacing protocol from the coronary sinus and high right atrium, respectively. Atrial models were stimulated with burst pacing from three locations in the proximity of each pulmonary vein to initiate re-entrant activation patterns. Five atria exhibited sustained activation patterns for at least 80 s. Models with short maximum action potential durations (APDs) were associated with sustained activation. Phase singularities were mapped across the atria sustained activation patterns. Regions with a low maximum conduction velocity (CV) were associated with tethering of phase singularities. A support vector machine (SVM) was trained on maximum local conduction velocity and action potential duration to identify regions that tether phase singularities. The SVM identified regions of tissue that could support tethering with 91% accuracy. This accuracy increased to 95% when the SVM was also trained on surface area., Conclusion: In a virtual patient cohort, local tissue properties, that can be measured (CV) or estimated (APD; using effective refractory period as a surrogate) clinically, identified regions of tissue that tether phase singularities. Combing CV and APD with atrial surface area further improved the accuracy in identifying regions that tether phase singularities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)